| 1. |
- Checknita, David, et al.
(författare)
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Associations of monoamine oxidase A gene first exon methylation with sexual abuse and current depression in women
- 2018
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Ingår i: Journal of neural transmission. - : SPRINGER WIEN. - 0300-9564 .- 1435-1463. ; 125:7, s. 1053-1064
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Tidskriftsartikel (refereegranskat)abstract
- Childhood physical abuse (PA) and sexual abuse (SA) interact with monoamine oxidase A (MAOA) gene polymorphism to modify risk for mental disorders. In addition, PA and SA may alter gene activity through epigenetic mechanisms such as DNA methylation, thereby further modifying risk for disorders. We investigated whether methylation in a region spanning the MAOA first exon and part of the first intron was associated with PA and/or SA, MAOA genotype, alcohol dependence, drug dependence, depression disorders, anxiety disorders, and conduct disorder. 114 Swedish women completed standardized diagnostic interviews and questionnaires to report PA and SA, and provided saliva samples for DNA extraction. DNA was genotyped for MAOA-uVNTR polymorphisms, and methylation of a MAOA region of interest (chrX: 43,515,544-43,515,991) was measured. SA, not PA, was associated with hypermethylation of the MAOA first exon relative to no-abuse, and the association was robust to adjustment for psychoactive medication, alcohol and drug dependence, and current substance use. SA and MAOA-uVNTR genotype, but not their interaction, was associated with MAOA methylation. SA associated with all measured mental disorders. Hypermethylation of MAOA first exon mediated the association of SA with current depression, and both methylation levels and SA independently predicted lifetime depression. Much remains to be learned about the independent effects of SA and MAOA-uVNTR genotypes on methylation of the MAOA first exon.
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| 2. |
- Checknita, Dave, et al.
(författare)
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Monoamine oxidase A genotype and methylation moderate the association of maltreatment and aggressive behaviour
- 2020
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Ingår i: Behavioural Brain Research. - : ELSEVIER. - 0166-4328 .- 1872-7549. ; 382
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Tidskriftsartikel (refereegranskat)abstract
- Background: The association between childhood maltreatment and subsequent aggressive behaviour is modified by monoamine oxidase A (MAOA) functional polymorphism (MAOA-uVNTR) genotype, MAOA-Long (MAOA-L) in females, MAOA-Short (MAOA-S) in males. Childhood maltreatment is associated with differential DNA methylation in several genes. Consistent with recent proposals, we hypothesized that the association of the interaction of MAOA genotype and maltreatment with aggressive behaviour is further moderated by methylation of a region of interest (ROI) spanning the first exon and partial first intron of MAOA.Method: The sample included 117 women and 77 men who completed interviews and questionnaires to report maltreatment and aggressive behaviour towards others and provided saliva samples for DNA extraction. The MAOA-uVNTR polymorphism was genotyped, and methylation of the MAOA ROI was assessed.Results: Following adjustment for substance misuse, psychoactive medication use, and in males tobacco use, the highest levels of aggressive behaviour were found among maltreated male carriers of MAOA-S with high levels of exonic methylation.Conclusion: Methylation levels within the MAOA ROI further contributed to the interaction of MAOA risk genotypes and maltreatment on aggressive behaviours among men.
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| 3. |
- Bamvita, Jean-Marie, et al.
(författare)
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Childhood predictors of adult psychopathy scores among males followed from age 6 to 33
- 2017
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Ingår i: Journal of criminal justice. - : Elsevier BV. - 0047-2352 .- 1873-6203. ; 53, s. 55-65
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Psychopathic traits are associated with multiple negative outcomes. The present prospective, longitudinal study identified associations of childhood factors with adult psychopathy scores.Methods: 311 men, aged, on average, 33 years, were assessed using the Psychopathy Checklist-Revised (PCL-R). Predictors included neighbourhood deprivation, parents' characteristics, teacher ratings of behaviour at ages 6, 10 and 12, and academic performance at age 12. Hierarchical linear regression models were computed to identify predictors at different ages of PCL-R total and facet scores.Results: Age 33 PCL-R total and facet scores were significantly, and independently, associated with father's and mother's criminality and mother's age at participant's birth when teacher ratings of childhood behaviours and mathematics marks were included in the models. Anxiety was negatively associated with facet 1 scores at age 6. At age 12, 22% of the variance in facet 2 scores was predicted by father's violent convictions, mother's age and criminal charges, and reactive aggression. Facet 3 scores were associated with mother's age (marginally), inattention, and reactive aggression. Facet 4 scores were associated with father's violent criminality, mother's age, conduct probleins, inattention, and reactive aggression.Conclusion: Etiological research and prevention programs should focus on antecedents of psychopathic traits present in early childhood.
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| 4. |
- Bendre, Megha, et al.
(författare)
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Associations Between MAOA-uVNTR Genotype, Maltreatment, MAOA Methylation, and Alcohol Consumption in Young Adult Males
- 2018
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Ingår i: Alcoholism. - : WILEY. - 0145-6008 .- 1530-0277. ; 42:3, s. 508-519
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundEpigenetic mechanisms are candidate moderators of the effect of maltreatment on brain and behavior. Interactions between maltreatment and the monoamine oxidase A upstream variable number tandem repeat genotype (MAOA-uVNTR) are associated with alcohol-related problems. However, presently it is not known whether DNA methylation moderates this association. The study focused on 53 young adult males and aimed to determine whether MAOA methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment, and whether alcohol consumption moderated the association of MAOA methylation with the interaction of MAOA-uVNTR and maltreatment. MethodsMAOA-uVNTR genotypes with 3 and > 3 repeats were categorized as short (S) and long (L), respectively. Data on maltreatment were obtained retrospectively, using self-reported questionnaires. DNA methylation of 16 candidate CpGs within part of the MAOA first exon and intron was assessed and grouped based on principal component analyses. Alcohol-related problems were assessed using the Alcohol Use Disorders Identification Test (AUDIT). Alcohol consumption was measured using AUDIT-C. Moderation effects were assessed and probed using the moderated moderation model and Johnson-Neyman's method, respectively. ResultsCarriers of the S allele, who experienced maltreatment and displayed lower Component 1 (mean of CpGs 13-16 in the first intron) MAOA methylation levels, reported higher AUDIT score in contrast to L-allele carriers. Carriers of the S allele, who reported higher AUDIT-C score and experienced maltreatment, displayed lower Component 3 (mean of CpGs 2-6 in the first exon) MAOA methylation levels than L-allele carriers. ConclusionsIntronic methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment. Alcohol consumption moderated the association of exonic methylation with the interaction of MAOA-uVNTR and maltreatment. These results suggest that epigenetic factors as well as genotype and maltreatment play a role in the development of alcohol misuse among young adult males.
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| 5. |
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| 6. |
- Checknita, Dave, et al.
(författare)
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Associations of Age, Sex, Sexual Abuse, and Genotype with Monoamine Oxidase A Gene Methylation
- 2021
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Ingår i: Journal of neural transmission. - : Springer Nature. - 0300-9564 .- 1435-1463. ; 128:11, s. 1721-1739
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Tidskriftsartikel (refereegranskat)abstract
- Epigenome-wide studies report higher methylation among women than men with decreasing levels with age. Little is known about associations of sex and age with methylation of monoamine oxidase A (MAOA). Methylation of the first exonic and partial first intronic region of MAOA has been shown to strengthen associations of interactions of MAOA-uVNTR genotypes and adversity with aggression and substance misuse. Our study examined associations of sex and age with MAOA first exon and intron methylation levels in 252 women and 157 men aged 14–73 years. Participants included adolescents recruited at a substance misuse clinic, their siblings and parents, and healthy women. Women showed ~ 50% higher levels of exonic, and ~ 15% higher intronic, methylation than men. Methylation levels were similar between younger (M = 22.7 years) and older (M = 46.1 years) participants, and stable across age. Age modified few associations of methylation levels with sex. MAOA genotypes modified few associations of methylation with sex and age. Higher methylation levels among women were not explained by genotype, nor interaction of genotype and sexual abuse. Findings were similar after adjusting for lifetime diagnoses of substance dependence (women = 24.3%; men = 34.2%). Methylation levels were higher among women who experienced sexual abuse than women who did not. Results extend on prior studies by showing that women display higher levels of methylation than men within first intronic/exonic regions of MAOA, which did not decrease with age in either sex. Findings were not conditioned by genotype nor interactions of genotype and trauma, and indicate X-chromosome inactivation.
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| 7. |
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| 8. |
- Robitaille, Marie-Pier, et al.
(författare)
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A prospective, longitudinal, study of men with borderline personality disorder with and without comorbid antisocial personality disorder
- 2017
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Ingår i: Borderline Personality Disorder and Emotion Dysregulation. - : BioMed Central (BMC). - 2051-6673. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Some evidence suggests that the prevalence of Borderline Personality Disorder (BPD) is elevated among male criminal offenders. It is not presently known whether offending, and violent offending, are limited to those presenting comorbid Antisocial Personality Disorder (ASPD) who have a childhood history of conduct problems and whether offending is linked to psychopathic traits. Methods: A community sample of 311 males followed from age 6 to 33 years, one third of whom had a criminal charge between ages 18 and 24, completed diagnostic interviews and the Psychopathy Checklist-Revised interview. Information on childhood included parent-reported family characteristics and teacher-rated of hurtful and uncaring behaviours, conduct problems, hyperactivity and inattention, and anxiety at age 6, 10, and 12 years. Health files were obtained as were records of criminal convictions from age 12 to 33. Results: At age 33, 4% of the men presented BPD and not ASPD, 16% ASPD and not BPD, 8% BPD + ASPD, and 72% neither disorder (ND). Comorbid disorders were common: BPD were distinguished by high levels of anxiety disorders, BPD and BPD + ASPD by depression disorders, and BPD, BPD + ASPD, and ASPD by substance dependence. Official files indicated use of health services by all participants. One-third of participants with BPD and BPD + ASPD acquired a diagnosis of a personality disorder. More than one-third of participants with BPD + ASPD obtained scores indicative of the syndrome of psychopathy. Convictions for violent crimes varied across groups: In adolescence, BPD none, BPD + ASPD 16%, ASPD 16%, and ND 3.6%; from age 18 to 33, BPD 18%, ASPD 19%, BPD + ASPD 52%, and ND 4.4%. Offenders with BPD + ASPD were convicted, on average, for four times more violent crimes than offenders with ASPD and seven times more than ND offenders. In childhood, men with BPD + ASPD and with ASPD had obtained similarly elevated ratings for disruptive behaviours as compared to ND. Conclusion: BPD comorbid with ASPD was associated with violent criminal offending in adolescence and most strongly in adulthood, elevated levels of psychopathic traits, and childhood disruptive behaviour. BPD showed similar characteristics but to a much less degree.
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